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Sean M Bagshaw, MD, MSc Division of Critical Care Medicine University of Alberta Comparing RRT Modalities: Does It Matter What You Use If The Job Is Done?
Sean M Bagshaw, MD, MSc
Division of Critical Care Medicine
University of Alberta
Comparing RRT
Modalities: Does It
Matter What You Use If
The Job Is Done?
Disclosure
• Consulting:
– Alere, Baxter, Gambro, Spectral
Diagnostics, Otsuka
• Speaking:
– Alere, Gambro, Otsuka
Does It Matter if the Job is Done?
Continuous OR Intermittent?
Continuous OR Intermittent?
WRONG QUESTION!
CRRT SLED IHD
Azotemic/Uremic Control
Time (day)
0 1 2 3 4 5 6 7
BU
N (
mg
/dL
)
0
20
40
60
80
100
120
CVVHIHDSLED
Liao et al Artif Organs 2003
Mehta et al KI 2001
10
15
20
25
30
35
1 2 3 4 5 6 7 8 9 10
Ure
a (
mm
ol/
L)
Day
CRRT IHD
Azotemic/Uremic Control
Volume Homestasis/Removal
Variable IHD SLED CRRT
Duration 3-5 6-8 20-24
Obligatory Intake 3500 mL 3500 mL 3500 mL
Urine output 100 100 100
Balance +3400 mL +3400 mL +3400 mL
Fluid removal (per hr)
1000 mL
2000 mL
3000 mL
4000 mL
200-350
400-600
600-1000
800-1300
125-150
250-350
375-500
500-650
40-50
83-100
125-150
150-200
Volume Homeostasis
Days
Me
an
%F
O
Bouchard et al KI 2009
Systemic Hemodynamics
• Therapeutic goals during RRT:
– Avoid rapid/large fluid compartment shifts
– Avoid intravascular depletion
– Avoid hypotension/decreases in cardiac output
– Avoid precipitation of arrhythmic episodes
– Avoid new/further ischemic injury to kidney
Augustine et al AJKD 2004; Manns et al NDT 1997
Hemodynamic Tolerance
Odds ratio Favours CRRT Favours IRRT
.1 .5 .25 1 2 4 8
Study
Odds ratio
(95% CI)
No. of events
CRRT IRRT
john (2001) 0.55 ( 0.12, 2.55) 9/20 6/10
gasparovic (2003) 0.19 ( 0.01, 4.11) 50/52 52/52
augustine (2004) 0.21 ( 0.07, 0.66) 5/40 16/40
vinsonneau (2006) 0.83 ( 0.54, 1.28) 61/175 72/184
Overall 0.66 ( 0.45, 0.96) 125/287 146/286
Bagshaw et al CCM 2007
Large ΔMAP
associated with
↓ renal recovery
IHD sessions complicated by hypotension ~ 17.5%
Instability during IHD can delay initiation or lead
to suboptimal sessions
Hemodiaf Study
IHD sessions complicated by hypotension ~ 39%
Instability during IHD can delay initiation or lead
to suboptimal sessions
Selby et al AJKD 2006
Myocardial Stunning
Variable Odds Ratio p
UF volume 1L 5.1 0.007
UF volume 1.5L 11.6
UF volume 2L 26.2
Max SBP Reduction 10 mmHg 1.8 0.002
Max SBP Reduction 20 mmHg 3.3
Max SBP Reduction 30 mmHg 6.0
Burton et al CJASN 2009
Anticoagulation/Bleeding Risk
Rabindranath et al Cochrane 2007
OR 1.03; 95% CI, 0.59-1.80
Specific ICU Subgroups
• Septic shock/multi-organ failure
• Fulminant hepatic failure (FHF)
• Brain injury (TBI, stroke, meningitis)
• Refractory congestive heart failure
• Post-cardiac surgical shock
Fulminant Hepatic Failure Subgroup
Davenport et al IJAO 1989; Davenport et al Contrib Nephrol 1991
Brain Injured Patients
0
10
20
30
40
50
60
0 4 24
Ho
un
sfie
ld U
nit
s
Time (hrs)
Grey White
0
10
20
30
40
50
60
0 4 24
Ho
un
sfiled
Un
its
Time (hrs)
Grey White
Ronco et al J Nephrol 1999
Continuous Intermittent
*
Does Modality Impact Survival?
Odds ratio
Favours CRRT Favours IRRT
.1 .5 .25 1 2 4 8
Study
Odds ratio
(95% CI)
No. of events
CRRT IRRT
simpson (1993) 0.50 ( 0.21, 1.20) 46/65 48/58
kierdorf (1994) 0.81 ( 0.36, 1.82) 29/48 34/52
john (2001) 1.00 ( 0.19, 5.24) 14/20 7/10
mehta (2001) 1.89 ( 1.01, 3.52) 54/84 40/82
gasparovic (2003) 1.67 ( 0.74, 3.78) 37/52 31/52
augustine (2004) 0.89 ( 0.35, 2.29) 27/40 28/40
uehlinger (2005) 0.91 ( 0.45, 1.85) 34/70 28/55
vinsonneau (2006) 0.95 ( 0.61, 1.48) 118/175 126/184
lins (unpublished) 0.83 ( 0.53, 1.31) 100/172 90/144
Overall 0.99 ( 0.78, 1.26) 459/726 432/677
Bagshaw et al CCM 2007; Rabindranath et al Cochrane 2007; Pannu et al JAMA 2008
Does Modality Impact Survival?
Lins et al NDT 2008
• SHARF 4 Trial:
– 9 centres in Belgium
– 316 critically ill patients with AKI (SCr ≥177 µmol/L)
RCT Design: Limitations
• No standardization of RRT practice
• Under-powered (sample size estimates)
• Selection bias:
– Exclusion of patients with hemodynamic instability
– Lack of CRRT machine availability
– Lack of trained personnel and/or institutional
expertise
RCT Design: Bias
• Failure of randomization/baseline differences
• Inadequate concealment
• Variations in applied RRT technology (i.e.
CAVH)
• Protocol modifications
• High cross-over between therapies (10-38%)
RCT Data: Generalizability
Trials performed over 2 decades
No standardized application of RRT
Cross-over - how can ITT analyses be interpreted?
Selected trials excluded CKD
Selected trials excluded hemodynamic instability
Are the patients in these RCTs truly
representative of our ICU population?
Odds ratio Favours CRRT Favours IRRT
.1 .5 .25 1 2 4 8
Study
Odds ratio
(95% CI)
No. of events
CRRT IRRT
mehta (2001) 0.50 ( 0.10, 2.42) 26/30 39/42
augustine (2004) 1.25 ( 0.24, 6.44) 5/13 4/12
uehlinger (2005) 1.38 ( 0.08, 23.17) 36/37 26/27
vinsonneau (2006) 0.29 ( 0.01, 7.25) 67/68 77/77
Overall 0.76 ( 0.28, 2.07) 134/148 146/158
Bagshaw et al CCM 2007
Does Modality Impact Recovery?
Does Modality Impact Recovery?
0
.2
.4
.6
.8
1
0 20 40 60 80 100
IRRT
CRRT
Days
Rec
over
y to
RR
T in
depe
nden
ce
89% vs. 65%; OR 3.33
(95% CI, 1.9-6.0), p<0.0001
Uchino et al IJAO 2007
ESKD: 8.3% vs. 16.5%
Adjusted-OR 2.6
(95% CI, 1.5-4.3)
Bell et al ICM 2007
Does Modality Impact Recovery?
Does Modality Impact Recovery?
Schneider et al ISICEM 2012 [Abstract]
ATN vs RENAL: Mortality
Variable ATN RENAL
All-patients n=1124 n=1508
Mortality 90 day (%) 44.7
Mortality 60 day (%) 52.5
SOFA score 3 or 4 (%) 36.9 70.0
Mortality 90 day (%) 47.5
Mortality 60 day (%) 79.8
* Survivors
ATN vs RENAL: Recovery
Variable ATN RENAL
*RRT dependence 28 day 45.2 13.3
*RRT dependence 60 day 24.6 ?
*RRT dependence 90 day ? 5.6
ATN vs RENAL: RRT-Free Days
6.5
17
0
5
10
15
20
25
ATN RENAL
RR
T-f
ree d
ays
ATN and RENAL?
• Possible explanations for the disparity:
– Chance/spurious finding
– Differences in patient characteristics
– Differences in timing of intervention
– Differences in RRT “bundle of care”
– Differences in processes of care
– Any combination of above…
• Are they important?
SLED/EDD
• Rationale:
– Lower solute/UF clearances
– Longer treatment duration
SLED/EDD aims to mimic CRRT
• Conclusion:
– SLED/EDD is a viable alternative to CRRT
– Logistically more simple
– Less expensive
Marshall et al KI 2001; Marshall et al NDT 2004; Kielstein et al AJKD 2004; Berbece et al KI 2006
SLED/EDD
• Observational single centre case-series:
– 37 critically ill patients (sepsis/cancer) intolerant of IHD
– 145 SLED sessions
• SLED details:
– Prescription: BFR ~ 200 mL/min, dialysate ~ 100 mL/hr
– Delivery: 10.4 hrs; dp-Kt/V 1.36 (n=9)
Results Proportion Sessions (%)
Session Stopped Early 34.5
Vasopressors Increased >50
Hypotensive Episodes 17
Blood Circuit Clotting 26
Marshall et al KI 2001
SLED/EDD
Kielstein et al AJKD 2004
• Phase II RCT
– 39 critically ill patients
– Oliguric AKI
• EDD (12 hr) vs. CRRT
– EDD by single-pass
• No differences:
– Hemodynamic tolerance
– Small-solute clearance
– UF volume
SLED/EDD
Parameter CVVH EDD P
Urea Removal (g) 73.1 71.8 NS
Creatinine Removal (g) 1.20 1.18 NS
B2M Removal (g) 0.29 0.15 <0.01
Kielstein et al AJKD 2004
Middle/Large MW Clearance
Time (day)
0 1 2 3 4 5 6 7
b2
M (
mg
/dL
)
0
1
2
3
4
5
6
CVVHIHDSLED
Liao et al Artif Organs 2003
SLED/EDD
• Observational single centre non-randomized pilot study:
– 23 critically ill patients requiring HD received SLED (165 sessions)
– 11 critically ill patients received CRRT (209 days)
Berbece et al KI 2006
Parameter SLED
(n=23)
CRRT
(n=11)
Treatment Days (Median) 6 13
RRT Time (hrs/day) 7.5 21.3
APACHE II score 24.4 26.3
Hypotension (% sessions) 14 -
EKR (mL/min) 28 29
Cost/wk (CDN$) 1431 2607-3089
SLED/EDD – Acid/Base Balance
Baldwin et al IJAO 2007; Baldwin et al ICM 2007
15
17
19
21
23
25
27
29
0 10 24 48 72
[HC
O3]
Time (hrs)
Serum Bicarbonate
CVVH EDDf
-4
-2
0
2
4
6
8
0 10 24 48 72
BE
Time (hrs)
Base Excess
CVVH EDDf
CRRT
(n=86)
SLED
(n=39) p
SOFA score 15.7 14.0 <0.001
MAP (mmHg) 74.1 (10.0) 76.4 (13.1) 0.34
Vasopressors (n, %) 62 (72.1) 19 (48.7) 0.01
UF Volume/session (mL) 1823 (1464) 1915 (1302) 0.74
MAP > 20% (n , %) 16 (18.6) 15 (38.5) 0.02
↑ Vasopressors (n, %) 34 (39.5) 10 (25.6) 0.13
Unstable sessions (n, %) 43 (50.0) 22 (56.4) 0.51
Fieghen et al BMC Nephrol 2010
SLED in VA/NIH ATN Trial
• Stratification to RRT modality by cSOFA score:
– Score >2 allocated to CRRT/SLED (55%)
– Score ≤2 allocated to IHD (45%)
• CRRT represented >95% of treatments
– Supported by additional observational studies/trials
• CRRT is the “Standard of care” for hemodynamically
unstable patients
• Clinicians do not yet believe SLED/EDD is equivalent to
CRRT (or have little experience)
ATN Trial NEJM 2008; Ronco et al Crit Care 2008; Uchino et al IJAO 2007; Bell et al ICM 2007
Health Technology Evaluation
HTA ~ Assumptions:
Accurate/current outcome data
Accurate/current costing data
Homogenous worldwide RRT practice
No differences in long-term outcomes
Bottomline ~ CRRT vs. IRRT:
Higher cost/treatment or /treatment day
Expenses for materials (i.e. fluids, anticoagulation, equipment)
Per patient treatment – no difference
Shorter duration AKI and need for RRT
RRT modality “choice” should never be driven by cost
alone
Mehta et al KI 2002; Vitale et al J Nephrol 2003; Manns et al CCM 2003; Tonelli et al, 2007 Available: wwwcadha.ca
Best (RRT Modality) Practice?
• When selecting RRT modality:
– Recognize the spectrum +/- shifts that occur in in
patients with critical illness +AKI → transition
• What are the Needs of the Patient?
• Hemodynamic stability? Acid/base control? Volume
homeostasis?
• What Are the Current Goals of Therapy?
• CRRT (as initial modality) → higher
likelihood of renal recovery
CRRT SLED IHD
Thank You For Your Attention!
Discussion
Questions?
